The overall basis for this proposal is the further understanding of the molecular biology of plasma and platelet factor XIII. Factor XIII is the proenzyme which, in its activated state, participates in the terminal phase of the coagulation of blood and catalyzes the chemical crosslinking of fibrin. The structure and function of factor XIII are the subject of this investigation. The goal of these studies is evaluation of the structural consequences of the activation of factor XIII, including the effect of removal of the activation peptide, the effect of the b subunit, and the effect of calcium ions. Development of radioimmunoassays for the subunits of the zymogen and for the enzyme are an important part of this project. These will be used to evaluate changes in antigenicity which occur during activation, to measure in vivo activation of factor XIII in various disease states, and to correlate protein concentrations with activity in factor deficiency and in various disease states. Other projects will include studies on the structure and function of plasma factor XIII b subunit, with emphasis on studying the binding of b subunit fragments to a subunit. Studies will be conducted to define the molecular role of calcium in factor XIII activation. Studies on patients with hereditary deficiency of factor XIII will be designed to probe the molecular abnormality(ies) in this disease. Studies with antibodies from patients with inhibitors to factor XIII will also be used to probe the structure of factor XIII molecules.